title: The inhibitory effect of a synthetic compound, (Z)-5-(2,4-dihydroxybenzylidene) thiazolidine-2,4-dione (MHY498), on nitric oxide-induced melanogenesis.
abstract: Nitric oxide (NO) and the NO/PKG signaling pathway play crucial roles in ultraviolet (UV)-induced melanogenesis, which is known to be related to the induction of tyrosinase. In an attempt to find a novel anti-melanogenic agent, we synthesized (Z)-5-(2,4-dihydroxybenzylidene)thiazolidine-2,4-dione (MHY498). The purpose of this study was to investigate the effect of MHY498 on NO levels and on the NO-mediated signaling pathway using an in vitro model of melanogenesis. MHY498 inhibited 200 μM sodium nitroprusside (SNP, a NO donor)-induced NO generation, dose-dependently and suppressed tyrosinase activity and melanin synthesis induced by SNP in B16F10 melanoma cells. To investigate the effect of MHY498 on NO-mediated signaling pathway, guanosine cyclic 3',5'-monophosphate (cGMP) activities were measured using a cGMP EIA Kit and western blotting was performed to determine the effects of MHY498 on the gene expressions of tyrosinase and microphthalmia-associated transcription factor (MITF). The increased activity of cGMP by SNP was reduced dose-dependently by pretreatment with MHY498. Furthermore, MHY498 suppressed the expressions of tyrosinase and MITF stimulated by SNP. This study shows that enhancement of tyrosinase gene expression via the cGMP pathway is a probable primary mechanism of NO-induced melanogenesis and that the NO-mediated signaling pathway with the expression of MITF enhances melanogenesis. In addition, MHY498 was found to scavenge NO and to suppress the activity of the NO-mediated signaling pathway, and thus, to subsequently down-regulate tyrosinase expression and melanogenesis. This study suggests that MHY498 is a promising anti-melanogenic agent that targets the NO-induced cGMP signaling pathway.
authors.affiliation: College of Pharmacy, Pusan National University, Geumjeong-Gu, Busan 609-735, Republic of Korea.
authors.forename: So Hee
authors.initials: SH
authors.lastname: Kim
authors.forename: Yeon Ja
authors.initials: YJ
authors.lastname: Choi
authors.forename: Kyoung Mi
authors.initials: KM
authors.lastname: Moon
authors.forename: Hye Jin
authors.initials: HJ
authors.lastname: Lee
authors.forename: Youngwoo
authors.initials: Y
authors.lastname: Woo
authors.forename: Ki Wung
authors.initials: KW
authors.lastname: Chung
authors.forename: Yuri
authors.initials: Y
authors.lastname: Jung
authors.forename: Sora
authors.initials: S
authors.lastname: Kim
authors.forename: Pusoon
authors.initials: P
authors.lastname: Chun
authors.forename: Youngjoo
authors.initials: Y
authors.lastname: Byun
authors.forename: Young Mi
authors.initials: YM
authors.lastname: Ha
authors.forename: Hyung Ryong
authors.initials: HR
authors.lastname: Moon
authors.forename: Hae Young
authors.initials: HY
authors.lastname: Chung
mesh_terms: D000818:Animals; D050882:CREB-Binding Protein / Q000378:metabolism; D002454:Cell Differentiation / Q000187:drug effects; D045744:Cell Line, Tumor; D000242:Cyclic AMP / Q000378:metabolism; D008543:Melanins / Q000378:metabolism; D051379:Mice; D014442:Monophenol Monooxygenase / Q000235:genetics / Q000378:metabolism; D009569:Nitric Oxide / Q000378:metabolism*; D010766:Phosphorylation / Q000187:drug effects; D045162:Thiazolidinediones / Q000138:chemical synthesis / Q000737:chemistry* / Q000494:pharmacology
chemical_list: C585780:(Z)-5-(2,4-dihydroxybenzylidene)thiazolidine-2,4-dione; D008543:Melanins; D045162:Thiazolidinediones; C500090:thiazolidine-2,4-dione; D009569:Nitric Oxide; D000242:Cyclic AMP; D014442:Monophenol Monooxygenase; D050882:CREB-Binding Protein